Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.146
Filtrar
1.
Br J Anaesth ; 124(3): e81-e91, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31980157

RESUMO

Exposure to anaesthetic drugs during the fetal or neonatal period induces widespread neuronal apoptosis in the brains of rodents and non-human primates. Hundreds of published preclinical studies and nearly 20 clinical studies have documented cognitive and behavioural deficits many months or years later, raising the spectre that early life anaesthesia exposure is a long-term, perhaps permanent, insult that might affect the quality of life of millions of humans. Although the phenomenon of anaesthesia-induced developmental neurotoxicity is well characterised, there are important and lingering questions pertaining to sex differences and neurodevelopmental sequelae that might occur differentially in females and males. We review the relevant literature on sex differences in the field of anaesthesia-induced developmental neurotoxicity, and present an emerging pattern of potential sex-dependent neurodevelopmental abnormalities in rodent models of human infant anaesthesia exposure.


Assuntos
Anestésicos/efeitos adversos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Animais , Ansiedade/induzido quimicamente , Apoptose/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtornos Cognitivos/induzido quimicamente , Metilação de DNA , Feminino , Humanos , Masculino , Síndromes Neurotóxicas/etiologia , Caracteres Sexuais
2.
Nat Med ; 25(9): 1428-1441, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501614

RESUMO

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.


Assuntos
Imunidade Celular , Neoplasias/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/genética , Animais , Ansiedade/sangue , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/fisiologia , Carcinógenos/toxicidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/psicologia , Corticosterona/sangue , Células Dendríticas/transplante , Regulação Neoplásica da Expressão Gênica , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/psicologia , Ativação Linfocitária/genética , Camundongos , Monitorização Imunológica/métodos , Neoplasias/induzido quimicamente , Neoplasias/genética , Neoplasias/psicologia , Receptores de Glucocorticoides/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/genética , Estresse Psicológico/terapia , Fatores de Transcrição/imunologia
3.
Oxid Med Cell Longev ; 2019: 6869350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428228

RESUMO

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERß, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERß than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.


Assuntos
Lilium/metabolismo , Menopausa/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/química , Receptor beta de Estrogênio/metabolismo , Feminino , Fulvestranto/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/análise , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/metabolismo
4.
S Afr Med J ; 109(6): 378-381, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31266554

RESUMO

The systemic fluoroquinolones (FQs) have recently been reported to be associated with significant side-effects in susceptible individuals. This has prompted the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) to issue warnings regarding their use. The FQs should not be used for common bacterial infections, such as urinary tract infections, travellers' diarrhoea and upper and lower respiratory tract infections, unless it is not possible to use another oral agent. There are situations, however, in which these agents are not only effective, but their benefit outweighs the risk. These include the management of conditions such as acute prostatitis, typhoid fever, prosthetic joint infections, multidrug-resistant tuberculosis, certain hospital-acquired infections and situations where the organism is susceptible to FQs, which could then be administered orally. Alternatively, the patient would have to be admitted to hospital for parenteral therapy.


Assuntos
Infecção Hospitalar/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Prostatite/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Febre Tifoide/tratamento farmacológico , Aneurisma Dissecante/induzido quimicamente , Ansiedade/induzido quimicamente , Fluoroquinolonas/uso terapêutico , Alucinações/induzido quimicamente , Humanos , Prótese Articular , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Psicoses Induzidas por Substâncias/etiologia , Ruptura/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Síndrome , Tendinopatia/induzido quimicamente
5.
Mediators Inflamm ; 2019: 7651383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281228

RESUMO

Many patients experience excellent physical recoveries after surgery; however, there are some of them who from suffer mood fluctuation, even depression. Postoperative depression may be resulted from cognitive dysfunction, pain, and a compromised immune system during the surgery. But there is a higher possibility that general anaesthesia may be responsible for the development of depression. Here, we employed one of the most used anaesthetics, propofol, in a mouse model to investigate whether this intravenous anaesthetic compound could cause depressive-like behavioural performance in mice. We found a single dose of propofol caused significant abnormal behavioural performance in tail suspension, forced swimming, and open field tests. We also examined the brain section of these mice and revealed that there was significant reduced expression of the CD11b protein, which demonstrated an inhibition of propofol on microglial function. We investigated the effect of propofol on synaptic protein, SYP, and found there was no notable influence on the protein expression. These above results suggested that propofol treatment might promote the depressive-like behaviours in mice via influencing the microglial cell function. Furthermore, we found the level of the IL-6 cytokine was significantly increased in the brain tissue, which might subsequently cause the activation of the transcriptional factor, STAT3. Our finding may provide a new perspective of further understanding the mechanism of anaesthetic drugs and deciphering the underlying mechanism of postoperative depression.


Assuntos
Depressão/induzido quimicamente , Microglia/efeitos dos fármacos , Microglia/fisiologia , Propofol/efeitos adversos , Anestesia Intravenosa , Animais , Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Antígeno CD11b/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Sinaptofisina/metabolismo
6.
Environ Int ; 131: 104927, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31326824

RESUMO

BACKGROUND: The association between air pollution exposure and emotional and behavioural problems in children is unclear. We aimed to assess prenatal and postnatal exposure to several air pollutants and child's depressive and anxiety symptoms, and aggressive symptoms in children of 7-11 years. METHODS: We analysed data of 13182 children from 8 European population-based birth cohorts. Concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters of ≤10 µm (PM10), ≤ 2.5 µm (PM2.5), and between 10 and 2.5 µm (PMcoarse), the absorbance of PM2.5 filters (PM2.5abs), and polycyclic aromatic hydrocarbons (PAHs) were estimated at residential addresses of each participant. Depressive and anxiety symptoms and aggressive symptoms were assessed at 7-11 years of age using parent reported tests. Children were classified in borderline/clinical range or clinical range using validated cut offs. Region specific models were adjusted for various socio-economic and lifestyle characteristics and then combined using random effect meta-analysis. Multiple imputation and inverse probability weighting methods were applied to correct for potential attrition bias. RESULTS: A total of 1896 (14.4%) children were classified as having depressive and anxiety symptoms in the borderline/clinical range, and 1778 (13.4%) as having aggressive symptoms in the borderline/clinical range. Overall, 1108 (8.4%) and 870 (6.6%) children were classified as having depressive and anxiety symptoms, and aggressive symptoms in the clinical range, respectively. Prenatal exposure to air pollution was not associated with depressive and anxiety symptoms in the borderline/clinical range (e.g. OR 1.02 [95%CI 0.95 to 1.10] per 10 µg/m3 higher NO2) nor with aggressive symptoms in the borderline/clinical range (e.g. OR 1.04 [95%CI 0.96 to 1.12] per 10 µg/m3 higher NO2). Similar results were observed for the symptoms in the clinical range, and for postnatal exposures to air pollution. CONCLUSIONS: Overall, our results suggest that prenatal and postnatal exposure to air pollution is not associated with depressive and anxiety symptoms or aggressive symptoms in children of 7 to 11 years old.


Assuntos
Poluentes Atmosféricos/análise , Ansiedade/epidemiologia , Depressão/epidemiologia , Exposição Ambiental/análise , Óxidos de Nitrogênio/análise , Material Particulado/análise , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Poluição do Ar/análise , Ansiedade/induzido quimicamente , Criança , Depressão/induzido quimicamente , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/análise , Tamanho da Partícula , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos
7.
Pharmacol Biochem Behav ; 184: 172742, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31348944

RESUMO

Ketamine has become increasingly popular in adolescent drug abusers worldwide. Meanwhile, alcohol is usually used by ketamine users. However, little work has been conducted to examine the chronic combined effects of ketamine and ethanol on adolescent brain. Here we probed into the effects of chronic administration of ketamine at recreational doses alone or combined with ethanol on behaviors and neuron damage in an adolescent rat model. 28-day old rats were treated with either 20 or 30 mg/kg ketamine plus or not plus 10% ethanol daily for 21 days. Depressive like behaviors, anxiety like behavior and memory impairment were tested using open field test, forced swimming test, elevated plus maze and Morris water maze. Apoptosis in prefrontal cortex (PFC) and hippocampus (HIP) were determined by the TdT-mediated dUTP Nick-End Labeling (TUNEL) and protein and mRNA levels of caspase-3, Bax and Bcl-2. Results show that co-application of ketamine and ethanol significantly increased immobility time in the forced swimming test, up-regulated TUNEL positive cells and both protein and mRNA expressions of caspase-3 and Bax, compared with the control group and ketamine and ethanol use alone groups in the PFC, but not in the HIP. Our study suggests that chronic co-administration of ketamine and ethanol results in depressive-like behavior and the caspase-dependent apoptosis in the PFC of adolescent rats' brains.


Assuntos
Anestésicos Dissociativos/farmacologia , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Hipocampo/efeitos dos fármacos , Ketamina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Anestésicos Dissociativos/administração & dosagem , Animais , Ansiedade/induzido quimicamente , Caspase 3/genética , Caspase 3/metabolismo , Depressores do Sistema Nervoso Central/administração & dosagem , Depressão/induzido quimicamente , Etanol/administração & dosagem , Hipocampo/metabolismo , Ketamina/administração & dosagem , Masculino , Memória/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
8.
BMC Gastroenterol ; 19(1): 85, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31195993

RESUMO

BACKGROUND: Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION: A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS: Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.


Assuntos
Antivirais/efeitos adversos , Ansiedade/induzido quimicamente , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Ribavirina/efeitos adversos , Ansiedade/virologia , Quimioterapia Combinada , Feminino , Hepatite C Crônica/psicologia , Hepatite C Crônica/virologia , Humanos , Pessoa de Meia-Idade
9.
Psychopharmacology (Berl) ; 236(5): 1653-1670, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31119329

RESUMO

RATIONALE: Mycobacterium vaccae (NCTC 11659) is an environmental saprophytic bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties. Previous studies have shown that whole, heat-killed preparations of M. vaccae prevent allergic airway inflammation in a murine model of allergic asthma. Recent studies also demonstrate that immunization with M. vaccae prevents stress-induced exaggeration of proinflammatory cytokine secretion from mesenteric lymph node cells stimulated ex vivo, prevents stress-induced exaggeration of chemically induced colitis in a model of inflammatory bowel disease, and prevents stress-induced anxiety-like defensive behavioral responses. Furthermore, immunization with M. vaccae induces anti-inflammatory responses in the brain and prevents stress-induced exaggeration of microglial priming. However, the molecular mechanisms underlying anti-inflammatory effects of M. vaccae are not known. OBJECTIVES: Our objective was to identify and characterize novel anti-inflammatory molecules from M. vaccae NCTC 11659. METHODS: We have purified and identified a unique anti-inflammatory triglyceride, 1,2,3-tri [Z-10-hexadecenoyl] glycerol, from M. vaccae and evaluated its effects in freshly isolated murine peritoneal macrophages. RESULTS: The free fatty acid form of 1,2,3-tri [Z-10-hexadecenoyl] glycerol, 10(Z)-hexadecenoic acid, decreased lipopolysaccharide-stimulated secretion of the proinflammatory cytokine IL-6 ex vivo. Meanwhile, next-generation RNA sequencing revealed that pretreatment with 10(Z)-hexadecenoic acid upregulated genes associated with peroxisome proliferator-activated receptor alpha (PPARα) signaling in lipopolysaccharide-stimulated macrophages, in association with a broad transcriptional repression of inflammatory markers. We confirmed using luciferase-based transfection assays that 10(Z)-hexadecenoic acid activated PPARα signaling, but not PPARγ, PPARδ, or retinoic acid receptor (RAR) α signaling. The effects of 10(Z)-hexadecenoic acid on lipopolysaccharide-stimulated secretion of IL-6 were prevented by PPARα antagonists and absent in PPARα-deficient mice. CONCLUSION: Future studies should evaluate the effects of 10(Z)-hexadecenoic acid on stress-induced exaggeration of peripheral inflammatory signaling, central neuroinflammatory signaling, and anxiety- and fear-related defensive behavioral responses.


Assuntos
Anti-Inflamatórios/imunologia , Anti-Inflamatórios/isolamento & purificação , Mycobacterium/imunologia , Mycobacterium/isolamento & purificação , Estresse Psicológico/imunologia , Estresse Psicológico/prevenção & controle , Animais , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/prevenção & controle , Colite/induzido quimicamente , Colite/imunologia , Colite/prevenção & controle , Medo/efeitos dos fármacos , Medo/fisiologia , Inflamação/imunologia , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , Microbiologia do Solo , Estresse Psicológico/induzido quimicamente
10.
Indian J Pharmacol ; 51(2): 123-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31142949

RESUMO

Fluoroquinolones are the commonly used antimicrobials in the treatment of urinary tract infection, bacterial diarrhea, and infections of soft tissue, bone, and joints. They may cause adverse effects ranging from gastrointestinal disturbances, headache, insomnia, and cutaneous reactions. Their rare adverse effects include phototoxicity, cardiotoxicity, arthropathy, and tendinitis. Among the fluoroquinolones, levofloxacin has more propensity to cause the central nervous system adverse effects such as headache, tremor, insomnia, dizziness, convulsions, psychosis, auditory, and visual hallucinations. A case of acute sinusitis in a young male treated with levofloxacin presented with tactile hallucination and acute anxiety reaction is reported for its rarity of occurrence. According to the Naranjo causality scale, the association of tactile hallucination and acute anxiety is a probable adverse drug reaction due to levofloxacin.


Assuntos
Antibacterianos/efeitos adversos , Ansiedade/induzido quimicamente , Alucinações/induzido quimicamente , Levofloxacino/efeitos adversos , Adulto , Humanos , Masculino , Sinusite/tratamento farmacológico , Adulto Jovem
11.
Int J Dev Neurosci ; 76: 6-16, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128204

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosis by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. Valproic acid (VPA), a teratogen is known to induce characteristic features related to ASD in rodents. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in prenatal VPA induced experimental ASD symptomatology in Wistar rats. The prenatal administration of VPA has induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, prenatal VPA-treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species, and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with pioglitazone significantly attenuated the prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the prenatal VPA-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, it may be concluded that pioglitazone may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autistic phenotypes in rats.


Assuntos
Anticonvulsivantes/toxicidade , Transtorno do Espectro Autista/prevenção & controle , Transtorno do Espectro Autista/psicologia , Hipoglicemiantes/farmacologia , Pioglitazona/farmacologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ácido Valproico/antagonistas & inibidores , Ácido Valproico/toxicidade , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Transtorno do Espectro Autista/induzido quimicamente , Química Encefálica/efeitos dos fármacos , Citocinas/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Comportamento Social
12.
Toxicol Ind Health ; 35(5): 358-367, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096887

RESUMO

The present study was planned to evaluate neurotoxic effects of ß-cyfluthrin in female Swiss albino mice. Two doses of ß-cyfluthrin, specifically, one-tenth of median lethal dose (LD50) and one-twentieth of LD50, were selected for the study. Open-field behaviour, exploratory behaviour and emotional status were affected, and animals showed anxiety-like behaviour after ß-cyfluthrin administration. Spatial learning was decreased using the Hebb-Wiliams maze. Acetylcholinesterase enzyme activity significantly decreased in the treated animals. The administration of ß-cyfluthrin caused increased lipid peroxidation (malondialdehyde) and decreased superoxide dismutase, catalase and glutathione peroxidase activity in brain tissue. In conclusion, ß-cyfluthrin caused neurotoxicity as well as oxidative damage in the brain of Swiss albino mice at the tested dose levels.


Assuntos
Ansiedade/induzido quimicamente , Aprendizagem/efeitos dos fármacos , Nitrilos/toxicidade , Piretrinas/toxicidade , Animais , Antioxidantes/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Síndromes Neurotóxicas/etiologia , Nitrilos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Piretrinas/administração & dosagem , Superóxido Dismutase/metabolismo
13.
Biomed Pharmacother ; 115: 108879, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035009

RESUMO

Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects.


Assuntos
Comportamento Animal/efeitos dos fármacos , Benzaldeídos/administração & dosagem , Benzaldeídos/farmacologia , Administração por Inalação , Agressão/efeitos dos fármacos , Animais , Ansiedade/induzido quimicamente , Depressão , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Odorantes
14.
Aerosp Med Hum Perform ; 90(5): 480-483, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023409

RESUMO

INTRODUCTION: Modafinil is a wakefulness-promoting stimulant that has been approved by the Republic of Singapore Air Force (RSAF) as a fatigue countermeasure medication since 2011. Each RSAF aircrew member must undergo a ground test to exclude operationally relevant adverse drug effects prior to consuming the medication for operational reasons. This study describes the RSAF's modafinil ground testing outcomes over a 7-yr period.METHODS: This is a retrospective case series of 243 RSAF aircrew members who underwent modafinil 100-mg test dosing over the 7-yr period from September 2011 to September 2018.RESULTS: The median age was 31 yr (range, 21-53 yr) and mean age was 31.7 yr ± 6.19 yr. Of the aircrew members, 234 (96.3%) were men and all were of Asian ethnicity. Of the subjects, 237 (97.5%) were medically cleared for the operational use of modafinil. Among the six (2.47%) who failed modafinil ground testing, headache (cumulative incidence, 1.65%), anxiety (cumulative incidence, 0.41%), diarrhea (cumulative incidence, 0.41%), and insomnia (cumulative incidence, 0.41%) were reported as the side effects experienced. None of the aircrew members experienced major adverse drug events.DISCUSSION: Our findings suggest a low occurrence of adverse drug effects among military aircrew members who undergo modafinil test dosing prior to using the drug operationally. To our knowledge, this is the single largest published case series of modafinil ground testing outcomes among Asian military aviators.Ooi T, Wong SH, See B. Modafinil as a stimulant for military aviators. Aerosp Med Hum Perform. 2019; 90(5):480-483.


Assuntos
Medicina Aeroespacial/métodos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Militares , Modafinila/efeitos adversos , Pilotos , Acidentes Aeronáuticos/prevenção & controle , Adulto , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Relação Dose-Resposta a Droga , Fadiga/prevenção & controle , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Estudos Retrospectivos , Singapura , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Vigília/efeitos dos fármacos , Adulto Jovem
15.
Pharmacol Biochem Behav ; 181: 1-8, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30946884

RESUMO

Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg orally (gavage) for 30 days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.


Assuntos
Ansiedade/induzido quimicamente , Memória/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Neurônios Serotoninérgicos/efeitos dos fármacos , Vareniclina/farmacologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Modelos Animais , Atividade Motora/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Agonistas Nicotínicos/administração & dosagem , Ratos , Ratos Wistar , Serotonina/metabolismo , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/métodos , Vareniclina/administração & dosagem , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Ácido gama-Aminobutírico/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-30946939

RESUMO

Alcohol abuse is a highly prevalent condition that substantially contributes to global morbidity and mortality. Most available pharmacological treatments offer little efficacy as relapse rates are high, due in part to the symptoms experienced during abstinence. The roles of oxidative stress and glutamatergic transmission in alcohol withdrawal have been demonstrated in several studies, suggesting that restoration of oxidative status and glutamatergic function may represent a new pharmacological target to prevent the behavioral and biochemical alterations observed during withdrawal. A well-known antioxidant and glutamatergic modulator, N-acetylcysteine (NAC), has shown promise in treating a variety of psychiatric conditions, including substance use disorders, and is a promising molecule in the management of alcohol withdrawal syndrome. Thus, the aim of this study was to investigate whether NAC is able to prevent the expression of behavioral and biochemical alterations induced by ethanol withdrawal in chronically exposed zebrafish. Animals were exposed to ethanol (1% v/v, 20 min) or control water, followed by treatment with NAC (1 mg/L, 10 min) or control water daily for 8 days; 24 h later, experimental animals were submitted to the novel tank test (NTT). Ethanol withdrawal decreased the distance traveled and increased the number of immobile episodes, indicating locomotor deficits; moreover, withdrawal decreased the number of entries and time spent in the top area, while increasing time spent in the bottom area, indicating anxiety-like behavior. Alcohol withdrawal also increased lipid peroxidation (TBARS) and decreased non-protein reduced sulfhydryl (NPSH) and superoxide dismutase (SOD) and catalase (CAT) activities. NAC attenuated these locomotor deficits and prevented the manifestation of anxiety-like behavior as well as the oxidative damage observed following ethanol withdrawal. Given its favorable safety profile, additional clinical and preclinical studies are warranted to unravel the long-term effects of NAC in the context of alcohol abuse and the exact mechanisms involved. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in substance abuse disorders.


Assuntos
Acetilcisteína/uso terapêutico , Etanol/efeitos adversos , Síndrome de Abstinência a Substâncias/prevenção & controle , Animais , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Peixe-Zebra
17.
Neurosci Lett ; 704: 153-158, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30974232

RESUMO

There are conflicting reports concerning the association of motor disabilities with increased risk of mental disorders. This investigation will provide a good understanding about defining the possible association between tremor and risk of anxiety and cognitive alterations. Beside, a secondary objective of the current study was to determine the effect of erythropoietin (EPO) on harmaline-induced motor and cognitive impairments. Male Wistar rats were used for the present study. The animal model of Esential tremor (ET) was established by the intraperitoneal injection of harmaline. EPO (5000 U/kg, i.p.) administered to the animals 1 h prior to harmaline injection. Exploratory, balance, anxiety related behaviors and cognitive function were assessed using footprint, open field, wire grip, rotarod and shuttle box tests. Findings demonstrated EPO ameliorated tremor scores that was induced by harmaline. Harmaline impaired cognitive functions of the treated rats, whereas EPO showed a promising effect against the cognitive impairments induced by harmaline. EPO can be offered as a potential neuroprotective agent in the treatment of patients with ET that manifest locomotor and cognitive impairments; however, further studies are needed to clarify the exact mechanisms.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Eritropoetina/farmacologia , Tremor Essencial/tratamento farmacológico , Harmalina , Fármacos Neuroprotetores/farmacologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Ansiedade/psicologia , Fenômenos Biomecânicos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Eritropoetina/uso terapêutico , Tremor Essencial/induzido quimicamente , Tremor Essencial/fisiopatologia , Tremor Essencial/psicologia , Comportamento Exploratório/efeitos dos fármacos , Marcha/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/uso terapêutico , Equilíbrio Postural/efeitos dos fármacos , Ratos Wistar
18.
Pharmacol Biochem Behav ; 181: 17-27, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30965047

RESUMO

Anxiety is a common symptom of schizophrenia. Ketamine, which acts as a noncompetitive antagonist of glutamatergic NMDA receptors by binding to the phencyclidine site, may induce schizophrenia-like symptoms and promote anxiogenic-like behaviour. The symptoms of anxiety in rodents can be measured by the elevated plus maze (EPM) test. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), as a neuroprotective and antiaddictive substance, produces pharmacological effects by influencing monoaminergic and glutamatergic activity, as previously demonstrated by us. The aim of the present study was to investigate the anxiolytic-like potential of 1MeTIQ after the administration of ketamine. These results were compared to the effects of olanzapine, an antipsychotic drug commonly used in the treatment of schizophrenia. We conducted the EPM test, during which the percentage of time spent in and the number of entries into the open arms were measured. In addition, locomotor activity was measured. Furthermore, we conducted biochemical analyses to verify changes in the levels of neurotransmitters and their metabolites in selected rat brain structures. Behavioural analyses showed that 1MeTIQ, similar to olanzapine, completely inhibited ketamine-induced anxiogenic effects in the EPM test. On the other hand, neurochemical data indicated that 1MeTIQ, as a reversible inhibitor of MAO, significantly blocked the dopamine MAO-dependent oxidation pathway, whereas olanzapine significantly increased the activity of this pathway. The results above suggest that the anxiolytic-like properties of 1MeTIQ are connected to its influence on the catabolism of dopamine, the elevation of serotonin concentrations and the reduction in the levels of noradrenaline.


Assuntos
Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Inibidores da Monoaminoxidase/farmacologia , Olanzapina/farmacologia , Tetra-Hidroisoquinolinas/farmacologia , Análise de Variância , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Norepinefrina/metabolismo , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo
19.
Psychopharmacology (Berl) ; 236(7): 2235-2242, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30868181

RESUMO

RATIONALE: N-[[1-(5-fluoropentyl)-1H-indazol-3-yl]carbonyl]-L-valine methyl ester (5F-AMB) is a synthetic cannabinoid that has been distributed recently. Although inhalation of 5F-AMB produces adverse effects, such as impaired memory and disturbed consciousness, in humans, the psychopharmacological effects of 5F-AMB in rodents have not been investigated. OBJECTIVES: We first examined the effects of intraperitoneal and intracerebroventricular injections of 5F-AMB on anxiety-like behavior and locomotor activity in the open field (OF) test and recognition memory in the novel object recognition test (NOR) in C57BL/6J mice. We also examined whether a cannabinoid 1 (CB1) receptor antagonist AM251 blocks the effects of 5F-AMB. We next examined the effects of 5F-AMB infusion into the medial prefrontal cortex (mPFC), a brain region associated with anxiety and memory, on these tests. RESULTS: Intraperitoneal injection of 5F-AMB (0.3 mg/kg) dramatically decreased locomotor activity in the OF, and this effect was partially reversed by AM251 (3 mg/kg). Intracerebroventricular infusion of 5F-AMB (10 nmol) produced an anxiolytic effect in the OF and impaired acquisition, but not retrieval, of recognition memory in the NOR, and these effects were blocked by co-infusion of AM251 (1.8 nmol). Bilateral intra-mPFC infusion of 5F-AMB (10 pmol/side) similarly produced impaired recognition memory acquisition, but no anxiolytic effect. CONCLUSIONS: The results demonstrate that centrally administered 5F-AMB produces anxiolytic effect and impaired recognition memory acquisition via activation of CB1 receptors, while systemic 5F-AMB severely impaired locomotor activity. The mPFC is involved in 5F-AMB-induced impairment of recognition memory acquisition. However, other brain region(s) may contribute to the 5F-AMB-induced anxiolytic effect.


Assuntos
Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Canabinoides/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , /efeitos dos fármacos , Animais , Ansiedade/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , /fisiologia
20.
Ecotoxicol Environ Saf ; 176: 34-41, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30921694

RESUMO

Air pollution by Diesel exhaust (DE) consists of gaseous compounds and diesel exhaust particles (DEPs). Previous studies show associations between prenatal exposure to diesel exhaust affects the central nervous system (CNS). However, there was not reported that these effects were caused by gaseous compounds, diesel exhaust particles, or both. A limited number of studies in rodent models have shown that exposure to DEPs can result in CNS. Here, we explored the effects of prenatal exposure to DEPs on anxiety and learning and memory in NMRI mice male offspring. Three groups of pregnant mice were exposed to 350-400 µg DEPs/m3 for 2, 4 and 6 h daily in a closed system room. We examined anxiety and learning and memory in 8-to-9-week-old male offspring using the Elevated plus maze and Morris water maze (MWM) test. Hippocampi were isolated after the behavioral tests and measured pro-inflammatory cytokines and N-methyl-D-aspartate (NMDA) receptor expression by quantitative RT-PCR analysis. Mice exposed to DEPs in utero showed deficits in the Elevated plus maze and Morris water maze test. In addition, DEPs exposed mice exhibited decreased hippocampal NR2A and NR3B expression. Taken together, our data suggest that maternal DEP exposure is associated with anxiety, disrupts learning and memory and reduction hippocampal NR2A and NR3B expression in male offspring.


Assuntos
Ansiedade/induzido quimicamente , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Memória/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Receptores de N-Metil-D-Aspartato/metabolismo , Emissões de Veículos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Animais , Citocinas/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Camundongos , Gravidez
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA